RA Effect on Cell Surface Molecules in Vivo

Retinoic Acid Effect on Cell Surface Molecules in Vivo

This study will follow a group of healthy male participants for about 18 weeks to see the effect of taking Acitretin on their immune cells

Study Overview

• Status: Withdrawn
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Acitretin

Detailed Description

Retinoids have been shown in in vitro and ex vivo models to have the ability to reverse latency reactivating the HIV reservoir and the potential for selective eradication of HIV-harbouring cells. We feel that acitretin shows significant potential as a potential adjuvant to current ART regimens, however, there is a lack of data to demonstrate that treatment with acitretin at normal are able to induce molecular and transcription changes consistent with the above activities. In order to provide a scientific basis for retinoid therapy in HIV infection, a Phase I trial of acitretin in human subjects is proposed.

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Male gender
2. Age 18 - 65
3. Able to provide informed consent
4. Willingness to participate in study treatment and follow-up
5. Willingness for serial phlebotomy and storage and future viro-immunological assays

Exclusion Criteria:

1. Female gender
2. Participants with a known hypersensitivity/allergy to the acitretin.
3. Participants who are actively participating in an experimental therapy study or who have received experimental therapy within the last 1 year.
4. Participants who are a poor medical risk because of other systemic diseases or active uncontrolled infections including HIV, Hepatitis B or C, and tuberculosis
5. Participants with impaired glucose tolerance including prediabetes or diabetes mellitus, dyslipidemia, or liver dysfunction
6. Previous or current history of mood disorder, psychosis, or suicidality
7. Participants currently receiving ongoing treatment with methotrexate, tetracyclines, or other retinoids

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Acitretin treatment

Drug: Acitretin; Acitretin will be provided to participants in the formulation Soriatane. Soriatane doses are oral tablets taken daily by the participant. Participants will then receive 35mg of oral acitretin (Soriatane) daily for 8 weeks during the intervention phase. Participants will be asked to return two months after completion of the acitretin course for clinical follow-up and additional phlebotomy for laboratory testing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Safety of Acitretin use in healthy volunteers will be assessed using safety labs and C-SSRS	up to 5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in α4β7 expression on peripherally circulating CD4 T cells	Absolute change in α4β7 expression on peripherally circulating CD4 T cells measured using flow cytometry	Serial phlebotomy measured over 5 months
Maximum Plasma Concentration [Cmax]	Serum concentrations measured by HPLC	Trough concentrations measured serially over 2 months of active treatment
Change in RIG-1 expression, p300 expression, mTOR expression	Absolute change in RIG-1 expression by qRTPCR, and change in p300 expression by western blot, change in mTOR expression by qRTPCR and mTOR total/phosphorylated by western blot	Serial phlebotomy measured over 5 months
Area Under the Curve [AUC]).	Serum concentrations measured by HPLC	Trough concentrations measured serially over 2 months of active treatment

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Investigators: Principal Investigator: Jonathan B Angel, MD, FRCPC, Ottawa Hospital Research Institute

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): January 7, 2019
• Primary Completion (ANTICIPATED): May 8, 2019
• Study Completion (ANTICIPATED): May 8, 2019

Study Registration Dates

• First Submitted: October 1, 2018
• First Submitted That Met QC Criteria: November 23, 2018
• First Posted (ACTUAL): November 27, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 4, 2020
• Last Update Submitted That Met QC Criteria: March 2, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Dermatologic Agents; Keratolytic Agents; Acitretin
• Other Study ID Numbers: 2018 0639

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No